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PDBsum entry 1f0y

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1f0y
Jmol
Contents
Protein chain
291 a.a. *
Ligands
CAA ×2
NAD ×2
Waters ×464
* Residue conservation analysis
PDB id:
1f0y
Name: Oxidoreductase
Title: L-3-hydroxyacyl-coa dehydrogenase complexed with acetoacetyl-coa and NAD+
Structure: L-3-hydroxyacyl-coa dehydrogenase. Chain: a, b. Synonym: hcdh. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: heart. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.210     R-free:   0.239
Authors: J.J.Barycki,L.K.O'Brien,A.W.Strauss,L.J.Banaszak
Key ref:
J.J.Barycki et al. (2000). Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase. J Biol Chem, 275, 27186-27196. PubMed id: 10840044 DOI: 10.1074/jbc.M004669200
Date:
17-May-00     Release date:   01-Sep-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q16836  (HCDH_HUMAN) -  Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial
Seq:
Struc:
314 a.a.
291 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.35  - 3-hydroxyacyl-CoA dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH
(S)-3-hydroxyacyl-CoA
Bound ligand (Het Group name = CAA)
matches with 96.00% similarity
+
NAD(+)
Bound ligand (Het Group name = NAD)
corresponds exactly
= 3-oxoacyl-CoA
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   6 terms 
  Biological process     small molecule metabolic process   11 terms 
  Biochemical function     oxidoreductase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M004669200 J Biol Chem 275:27186-27196 (2000)
PubMed id: 10840044  
 
 
Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase.
J.J.Barycki, L.K.O'Brien, A.W.Strauss, L.J.Banaszak.
 
  ABSTRACT  
 
l-3-Hydroxyacyl-CoA dehydrogenase reversibly catalyzes the conversion of l-3-hydroxyacyl-CoA to 3-ketoacyl-CoA concomitant with the reduction of NAD(+) to NADH as part of the beta-oxidation spiral. In this report, crystal structures have been solved for the apoenzyme, binary complexes of the enzyme with reduced cofactor or 3-hydroxybutyryl-CoA substrate, and an abortive ternary complex of the enzyme with NAD(+) and acetoacetyl-CoA. The models illustrate positioning of cofactor and substrate within the active site of the enzyme. Comparison of these structures with the previous model of the enzyme-NAD(+) complex reveals that although significant shifting of the NAD(+)-binding domain relative to the C-terminal domain occurs in the ternary and substrate-bound complexes, there are few differences between the apoenzyme and cofactor-bound complexes. Analysis of these models clarifies the role of key amino acids implicated in catalysis and highlights additional critical residues. Furthermore, a novel charge transfer complex has been identified in the course of abortive ternary complex formation, and its characterization provides additional insight into aspects of the catalytic mechanism of l-3-hydroxyacyl-CoA dehydrogenase.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. L-3-Hydroxyacyl-CoA dehydrogenase complexed with the substrate, 3-hydroxybutyryl-CoA. The ribbon diagram depicts the two-domain structure of an HAD subunit, with the first 200 amino acids comprising the NAD +-binding domain and the remaining residues comprising the C-terminal domain. 3-Hydroxybutyryl-CoA, shown in ball and stick representation, binds within the cleft between these two domains. The adenine moiety of coenzyme A is positioned adjacent to the helix-turn-helix tail ( 2- 3) of the NAD^+-binding domain, and the acyl chain is within the enzyme active site.
Figure 4.
Fig. 4. Schematic of the 3-hydroxybutyryl-CoA-binding site. Hydrogen bonds involved in binding of the substrate, 3-hydroxybutyryl-CoA, to the apoenzyme are represented as dashed lines, with residues of the opposing subunit of the dimer indicated with an asterisk.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 27186-27196) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20530902 J.Arima, A.Uesumi, H.Mitsuzumi, and N.Mori (2010).
Biochemical characterization of L-carnitine dehydrogenases from Rhizobium sp. and Xanthomonas translucens.
  Biosci Biotechnol Biochem, 74, 1237-1242.  
20054534 J.Parkot, H.Gröger, and W.Hummel (2010).
Purification, cloning, and overexpression of an alcohol dehydrogenase from Nocardia globerula reducing aliphatic ketones and bulky ketoesters.
  Appl Microbiol Biotechnol, 86, 1813-1820.  
  18323616 Y.Asada, C.Kuroishi, Y.Ukita, R.Sumii, S.Endo, T.Matsunaga, A.Hara, and N.Kunishima (2008).
Crystallization and preliminary X-ray crystallographic analysis of rabbit L-gulonate 3-dehydrogenase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 228-230.  
16169737 A.Li, T.Itoh, T.Taguchi, T.Xiang, Y.Ebizuka, and K.Ichinose (2005).
Functional studies on a ketoreductase gene from Streptomyces sp. AM-7161 to control the stereochemistry in medermycin biosynthesis.
  Bioorg Med Chem, 13, 6856-6863.  
16176262 S.Y.Yang, X.Y.He, and H.Schulz (2005).
3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease.
  FEBS J, 272, 4874-4883.  
15229654 M.Ishikawa, D.Tsuchiya, T.Oyama, Y.Tsunaka, and K.Morikawa (2004).
Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex.
  EMBO J, 23, 2745-2754.
PDB codes: 1wdk 1wdl 1wdm
12192068 C.A.Bottoms, P.E.Smith, and J.J.Tanner (2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
  Protein Sci, 11, 2125-2137.  
11559359 X.Y.He, G.Merz, Y.Z.Yang, P.Mehta, H.Schulz, and S.Y.Yang (2001).
Characterization and localization of human type10 17beta-hydroxysteroid dehydrogenase.
  Eur J Biochem, 268, 4899-4907.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.